The Effects of a CXCR2 Antagonist on Postnatal Systemic Inflammation-Disrupted Alveolar Development in a Rat Model of BPD

Background: Bronchopulmonary dysplasia (BPD) is the most common morbidity suffered by surviving preterm infants and is associated with adverse pulmonary and neurodevelopmental outcomes. Inflammation plays a pivotal role in the pathogenesis of BPD. An influx of inflammatory cells and neutrophil-derived chemokines has been implicated in the development of BPD. A competitive CXCR2 receptor antagonist reduces neutrophil activation and influx into tissues.

Objective: To evaluate the effects of a CXCR2 antagonist on reducing postnatal systemic inflammation and consequently developing BPD in rat model.

Methods: Lipopolysaccharide(LPS) was administered to the amniotic fluid on E20, which corresponds to the late canalicular stage of rat lung development. LPS and a CXCR2 receptor antagonist were administered intraperitoneally on P1, P3, and P5, which correspond to the saccular and early alveolar stages. On P7 and P14, bronchoalveolar lavage fluid (BALF) and peripheral blood (PB) were collected from the rat pups. To assess alveolar development, four random, non-overlapping fields per animal in two distal lung sections were studied at 100X magnification.

Results: Early postnatal LPS administration significantly increased neutrophil counts in BALF and PB and disrupted alveolar development, whereas prenatal LPS alone did not. The CXCR2 antagonist significantly attenuated neutrophil increases in BALF and PB and restored alveolar development in the rat pups exposed to early ponstnatal LPS.

Conclusion: These results suggest that a CXCR2 receptor antagonist restores alveolar development by alleviating pulmonary and systemic inflammation induced by early postnatal LPS.